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Background: Risk factors for non-communicable diseases (NCDs, cardiovascular diseases, cancers, chronic respiratory diseases, diabetes, and mental disorders) arise in adolescence but are mostly framed as relevant to health in adulthood; little is known about the relationship between co-occurring NCD risks and mental wellbeing in young people. This study aims to describe the prevalence and co-occurrence of distinct NCD risk factors, and how they relate to current mental wellbeing amongst adolescents in Indonesia, a young and populous country where NCD burden is increasing rapidly., Methods: We assessed NCD risk and mental wellbeing amongst 1,331 school-based 16-18-year-olds in Jakarta (N = 609) and South Sulawesi (N = 722). Five domains of NCD risk (adiposity, substance use, physical inactivity, excess sedentary time, and diet) were either measured or self-reported. In Jakarta, we also measured blood glucose, triglycerides, cholesterol, and blood pressure. Wellbeing was assessed using three indicators: general quality of life (QoL), physical function QoL, and psychological distress. We used linear regression to estimate the associations between co-occurring risks and wellbeing, adjusted for covariates of wellbeing: province, sex, socioeconomic status, and religion., Results: NCD risk clustering was common, and more than half of adolescents had co-occurring risks in 3 or more of the 5 domains (58.9% (95%CI 53.7-63.9)). Adolescents with any NCD risk were more likely to report psychological distress, with this relationship most pronounced in those with excess sedentary time spent on video gaming and computer use. A higher number of NCD risk factors was associated with poorer psychological wellbeing and decreased general and physical function QoL. In the Jakarta subsample, reduced HDL and raised blood glucose was associated with psychological distress; and a higher number of risk biomarkers was associated with lower physical function QoL., Conclusions: Our analysis also shows that these NCD risks (both individual risks and co-occurring risk count) are related to poorer profiles of mental wellbeing in adolescents, after adjusting for likely confounders., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Alfred Hospital Human Research Ethics Committee, Melbourne, Australia (approval number 114/17) and the Ethics Committee of the Faculty of Medicine, Universitas Indonesia (approval number 714/UN2.F1/ETIK/2017). All participants needed written informed consent from a parent or guardian, and to give their own informed assent, to participate in data collection. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

ATP-activated P2X3 receptors play a pivotal role in chronic cough, affecting more than 10% of the population. Despite the challenges posed by the highly conserved structure of P2X receptors, efforts to develop selective drugs targeting P2X3 have led to the development of camlipixant, a potent, selective P2X3 antagonist. However, the mechanisms of receptor desensitization, ion permeation, and structural basis of camlipixant binding to P2X3 remain unclear. Here, we report a cryo-EM structure of camlipixant-bound P2X3, revealing a previously undiscovered selective drug-binding site in the receptor. Our findings also demonstrate that conformational changes in the upper-body domain, including the turret and camlipixant-binding pocket, play a critical role: turret opening facilitates P2X3 channel closure to a radius of 0.7 Å, hindering cation transfer, while turret closure leads to channel opening. Structural and functional studies combined with molecular dynamics simulations provide a comprehensive understanding of camlipixant's selective inhibition of P2X3, offering a foundation for future drug development targeting this receptor., Competing Interests: Conflict of Interest declaration PPN, SS, IH, SA, and JS work for ELANCO. This work was funded by a grant to RS from ELANCO., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to estimate the prevalence of mental health problems and identify potential risk and protective exposures for adolescents in Indonesia., Methods: An innovative sampling approach was applied to simultaneously recruit school- and community-based adolescents aged 16-18 years old from Jakarta (urban megacity) and South Sulawesi (remote province). We used multistage cluster sampling for in-school (N = 1,337) and respondent driven sampling for out-of-school (N = 824) adolescents. Mental health was measured using two validated scales: Kessler-10 and Center for Epidemiologic Studies Depression Scale-Revised. Psychiatric interviews were conducted in a subsample (N = 196) of students from Jakarta to validate the self-report scales., Results: The estimated population prevalence of psychological distress and depression were 24.3% (95% CI = 21.5-27.2) and 12.6% (10.5-14.4) for in-school and 23.7% (20.7-26.7) and 23.5% (20.4-26.5) for out-of-school adolescents, respectively. In participants who completed a psychiatric interview, common psychiatric morbidities were social anxiety, depression, and suicidality. Compared to in-school females, male in-school adolescents reported a lower prevalence of psychological distress (16.9% (13.1-20.7) vs. 30.4% (26.4-34.4)) and depression (10.1% (7.2-13.1) vs. 14.6 (11.4-17.8)). By contrast, for out-of-school adolescents, males reported a higher prevalence of psychological distress (25.2% (21.6-28.9) vs. 20.2% (15.1-25.3)) and depression (26.3% (22.5-30.1) vs. 16.9% (11.8-21.9)). In-school adolescents who did not seek healthcare despite a perceived need were more likely to report psychological distress and depression., Discussion: Adolescent mental health problems are highly prevalent in Indonesia, with substantial variation by gender, geography, and school enrolment. This study and its approach to sampling and measurement may serve as a model to improving mental health surveillance across other settings., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors have no competing interest to declare.

Background We explored the impact of the COVID-19 pandemic on the prevalence and outcomes of takotsubo syndrome (takotsubo) using the National Inpatient Sample (NIS) to compare trends before and during the pandemic. Methods This retrospective study examined data from over 137 million admissions during 2017-2018 (pre-pandemic) and 2020-2021 (pandemic). Results Our analysis revealed a marked increase in takotsubo prevalence, from 109.07 to 131.19 per 100,000 admissions over each two-year period. The majority of patients were elderly females, with a notable rise in associated comorbidities such as hypertension and diabetes during the pandemic. Mortality among takotsubo patients rose significantly, with an adjusted odds ratio of 1.28. Patients with concurrent COVID-19 infection had a mortality rate of 23.02%, significantly higher than 7.61% for those without. The length of hospital stays also increased, particularly among COVID-19 patients. Interestingly, the odds of developing takotsubo were lower in COVID-19 patients than in non-infected individuals, suggesting a broader pandemic-related stress impact. Conclusion Our findings highlight a complex interaction between viral infections, stress, and cardiovascular health, underscoring the need for integrated care strategies during global health crises., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tran et al.)

Background: Kombucha is a widely consumed fermented beverage produced by fermenting sweet tea with a symbiotic culture of bacteria and yeast (SCOBY). The dynamic nature of microbial communities in SCOBY may pose challenges to production scale-up due to unpredictable variations in microbial composition. Using identified starter strains is a novel strategy to control microorganism composition, thereby ensuring uniform fermentation quality across diverse batches. However, challenges persist in the cultivation and maintenance of these microbial strains. This study examined the potential of microencapsulated kombucha fermentation starter cultures, specifically Komagataeibacter saccharivorans, Levilactobacillus brevis and Saccharomyces cerevisiae, through spray-drying and freeze-drying., Results: Maltodextrin and gum arabic-maltodextrin were employed as carrier agents. Our results revealed that both spray-dried and freeze-dried samples adhered to physicochemical criteria, with low moisture content (2.18-7.75%) and relatively high solubility (65.75-87.03%) which are appropriate for food application. Freeze-drying demonstrated greater effectiveness in preserving bacterial strain viability (88.30-90.21%) compared to spray drying (74.92-78.66%). Additionally, the freeze-dried starter strains demonstrated similar efficacy in facilitating kombucha fermentation, compared to the SCOBY group. The observations included pH reduction, acetic acid production, α-amylase inhibition and elevated total polyphenol and flavonoid content. Moreover, the biological activity, including antioxidant potential and in vitro tyrosinase inhibition activity, was enhanced in the same pattern. The freeze-dried strains exhibited consistent kombucha fermentation capabilities over a three-month preservation, regardless of storage temperature at 30 or 4 °C., Conclusion: These findings highlight the suitability of freeze-dried starter cultures for kombucha production, enable microbial composition control, mitigate contamination risks and ensure consistent product quality. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Introduction: Early parenting services in Australia offer brief structured residential programs to address moderate to severe non-psychotic mental health problems among women and unsettled infant/toddler behaviours. The aims were to (1) estimate the immediate and medium-term impact of a five-night psychoeducational residential early parenting program on postpartum depressive symptoms and (2) identify the factors associated with improvement or worsening of postpartum depressive symptoms after completing the program and six weeks post-discharge., Methods: Audit of routinely collected medical record data from pre-admission, pre-discharge and post-discharge assessments of a consecutive cohort of women admitted, with their infants/toddlers in a 15-month period to Masada Private Hospital Early Parenting Centre. Data included structured questions assessing: demographic characteristics, access to family and social support, past and current mental health problems, reproductive and obstetric health, chronic health conditions, breastfeeding problems, coincidental major life events, health risk behaviours and infant/toddler feeding, sleeping and crying behaviours. Standardised instruments included the Partner Interaction after Birth Scale (PIBS), the MacLean Screening Instrument for Borderline Personality Disorder (MSI-BPD), Modified Fatigue Assessment Scale (FAS) and selected items from the Karitane Parenting Confidence Scale. The primary outcomes were Edinburgh Postnatal Depression Scale scores at pre-discharge and follow up assessments. Data were analysed using multinomial logistic regression models in which individual and psychosocial characteristics at pre-admission were included as predictors of the likelihood of the changes of the outcomes from pre-admission to pre-discharge and follow up., Results: Complete data from 1220 of 1290 (95%) eligible women were available to assess pre-admission to pre-discharge and from 559 (45.8%) to assess pre-discharge to six-week follow-up changes. The mean pre-admission EPDS score was 11.7 (95% CI: 11.5; 12.0), pre-discharge it was 7.1 (95% CI: 6.9; 7.4) and at six-week follow up it was 5.7 (95% CI: 5.3; 6.1). We found that almost all women experienced a clinically meaningful and rapid improvement in depressive symptoms of at least this magnitude (reduction in mean EPDS scores of 4.6 points from pre-admission to pre-discharge (five nights) and a further reduction of 1.2 points pre-discharge to follow up) (six weeks) and we identified an interpretable set of risk factors for symptoms that did not improve or worsened. The adverse outcomes were associated with having symptoms of borderline personality disorder, a partner experienced as lacking kindness and care, coincidental adverse events and having a child younger than six months., Conclusion: Residential early parenting programs, which take a psycho-educational approach to strengthening caregiving skills, maximising agency, and reducing helplessness, have a rapid beneficial effect on women's postpartum depressive symptoms. These programs provide a valuable and effective component of comprehensive mental health services. Long-term dialectical behaviour therapy is indicated for women with borderline personality disorder traits for whom early parenting programs alone are insufficient to improve depressive symptoms., (© 2024 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Direct-acting oral anticoagulants (DOACs) are recommended to reduce risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). However, DOAC dosing inconsistent with FDA-approved product labels is common and associated with poor clinical outcomes., Objectives: Identify DOAC dosing inconsistent with FDA-approved product labels in ambulatory care patients with NVAF; identify variables associated with dosing lower and higher than label., Design: Retrospective analysis using electronic health records from nine US healthcare systems., Patients: Adults with NVAF receiving DOAC therapy in 2022., Main Measures: Rates of label-inconsistent dosing; multivariable regression analysis to identify demographic and clinical variables associated with dosing lower and higher than label., Key Results: Among 51,128 NVAF patients (56.1% male, 94.3% White, mean [SD] age 73.5 [10.5] years), 5008 (9.8%) were prescribed label-inconsistent doses of DOACs (6.8% lower and 3.0% higher than label). Age ≥ 75 years, renal impairment, and hypertension were significantly associated with inconsistent dosing both higher and lower than label. Female sex and higher weight were significantly associated with dosing lower than label, as were heart failure, vascular or liver disease, and bleeding history. Dosing higher than label was significantly associated with male sex, race (African American/Black), weight < 60 kg, and use of drugs with potential drug-drug interactions. When prescribed by primary care physicians, DOAC doses were 37% (95% CI, 27-49%) more likely to be lower than label and 30% (95% CI, 16-46%) more likely to be higher than label than when prescribed by cardiologists or electrophysiologists. Label-inconsistent dosing varied (6.7 to 15.8%) across participating systems., Conclusions: DOAC dosing inconsistent with label varied by demographics, clinical characteristics, prescriber specialty, and healthcare system, suggesting a need to monitor and assess dosing decisions in NVAF. Identification of variables associated with dosing inconsistencies may enable targeted interventions to ensure label-consistent dosing in vulnerable populations., (© 2024. The Author(s).)

One in three patients admitted to intensive care will sustain a pressure injury (PI) from a medical device. These injuries are painful and when on the face, head or neck they can result in permanent disfigurement. Preliminary evidence of the efficacy of hyper-oxygenated fatty acids (HOFAs) to prevent facial pressure injuries from medical devices is promising; however, the feasibility of incorporating HOFAs into current standard care to prevent PI from a medical device of the face, head and neck has not been extensively explored. It is intended that the findings from this phase II feasibility study will inform the design of a larger phase III trial, by addressing two primary aims: (1) to assess the feasibility of incorporating HOFAs into standard care to prevent device-related pressure ulcers of the skin associated with the face, head and neck assess the feasibility and (2) efficacy preliminary effectiveness of HOFA. This feasibility study is an investigator-initiated mixed method study incorporating a multi-centre randomised controlled trial of using HOFAs as an adjunct to standard pressure injury prevention and care, compared with standard care alone to prevent facial, head or neck from medical devices among adults admitted to intensive care. The primary outcome of interest is the incidence of facial, head or neck pressure injuries during the first 14 days in intensive care. Secondary outcomes include PI staging, medical device exposure and intensive care and hospital outcomes. The primary analysis will be undertaken using Cox's Proportional Hazards model, and due to the exploratory nature of this phase II trial, efficacy will be based on a one-sided p-value for superiority set at 0.10. Type I and Type II error rates are set at 20%; therefore, a total sample size of 196 study participants is planned. To explore the feasibility of incorporating HOFA into usual care and to design a larger phase III trial, we will aim to interview between 10 and 20 nurses across participating intensive care unit sites. Pressure injuries of the face, head or neck from medical devices, among adults admitted to intensive care, are considered preventable. This phase II study will investigate the feasibility and efficacy of HOFAs as an adjunct to standard care. Importantly, we aim to inform the development of a larger phase III trial., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Sialic acids play crucial roles in cell surface glycans of both eukaryotic and prokaryotic organisms, mediating various biological processes, including cell-cell interactions, development, immune response, oncogenesis and host-pathogen interactions. This review focuses on the β-anomeric form of N-acetylneuraminic acid (Neu5Ac), particularly its binding affinity towards various proteins, as elucidated by solved protein structures. Specifically, we delve into the binding mechanisms of Neu5Ac to proteins involved in sequestering and transporting Neu5Ac in Gram-negative bacteria, with implications for drug design targeting these proteins as antimicrobial agents. Unlike the initial assumptions, structural analyses revealed significant variability in the Neu5Ac binding pockets among proteins, indicating diverse evolutionary origins and binding modes. By comparing these findings with existing structures from other systems, we can effectively highlight the intricate relationship between protein structure and Neu5Ac recognition, emphasizing the need for tailored drug design strategies to inhibit Neu5Ac-binding proteins across bacterial species., (open access.)

Introduction: Older adults can face challenges when seeking care from emergency departments (EDs) due to presenting with multiple comorbidities and non-specific symptoms. Psychosocial care is a possible target to help improve ED care for this population. It is possible that digital health technologies can be implemented within emergency settings to improve the provision of psychosocial care. However, it is unclear what the barriers and facilitators are to implementing digital psychosocial interventions for older adults presenting to the ED. Therefore, the scoping review aims to determine what are these barriers and facilitators., Methods and Analysis: The scoping review will be conducted in line with the Joanna Briggs Institute guidelines and will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. The databases Medline, Embase, PsycINFO and Scopus will be searched. The search strategy will be developed in consultation with a specialist research librarian and will cover three key concepts: EDs, digital health technologies and older adults. Additionally, the first 100 hits of a Google Scholar search will be screened for inclusion. We will include both qualitative and quantitative studies that investigate ED digital interventions for psychosocial care where the primary focus is the views, attitudes, experiences and perceptions of patients, families and staff. After extracting all data, analysis and synthesis will follow the 'best-fit framework synthesis' approach and the Theoretical Domains Framework will be used to identify barriers and facilitators., Ethics and Dissemination: Ethics approval is not required for this scoping review since only publicly available data will be analysed and appraised. The findings of the scoping review will be disseminated through peer-reviewed publications and conference presentations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Comorbidities are common in fracture patients, but the interaction between fracture and comorbidities remains unclear. This study aimed to define specific multimorbidity clusters in older adults and quantify the association between the multimorbidity clusters and fracture risk., Methods: This nationwide cohort study includes 1.7 million adults in Denmark aged ≥50 years who were followed from 2001 through 2014 for an incident low-trauma fracture. Chronic diseases and fractures were identified from the Danish National Hospital Discharge Register. Latent class analysis and Cox's regression were conducted to define the clusters and quantify fracture risk, respectively., Results: The study included 793 815 men (age: 64 ± 10) and 873 524 women (65.5 ± 11), with a third having ≥1 chronic disease. The pre-existent chronic diseases grouped individuals into low-multimorbidity (80.3% in men, 83.6% in women), cardiovascular (12.5%, 10.6%), malignant (4.1%, 3.8%), diabetic (2.4%, 2.0%) and hepatic clusters (0.7%, men only). These clusters distinguished individuals with advanced, complex, or late-stage disease from those having earlier-stage disease. During a median follow-up of 14 years (IQR: 6.5, 14), 95 372 men and 212 498 women sustained an incident fracture. The presence of multimorbidity was associated with a significantly greater risk of fracture, independent of age and sex. Importantly, the multimorbidity clusters had the highest discriminative performance in assessing fracture risk, whereas the strength of their association with fracture risk equalled or exceeded that of both the individual chronic diseases most prevalent in each cluster and of counts-based comorbidity indices., Conclusions: Future fracture prevention strategies should take comorbidities into account. Multimorbidity clusters may provide greater insight into fracture risk than individual diseases or counts-based comorbidity indices., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We aimed to determine the effect of coping self-efficacy on thoughts of self-harm among adolescents attending high school in Hanoi, Vietnam. Longitudinal data were collected using the Center for Epidemiologic Studies Depression Scale Revised and the Coping Self-Efficacy Scale among 552 Year 10 students. The prevalence of thoughts of death and/or self-injury on at least 1 day in the past week was 16.9% at baseline and 14.5% at 8-month follow-up. When baseline coping self-efficacy was greater by one standard deviation, the odds of having thoughts of self-harm at follow-up were reduced by 42%. Our findings suggest that school-based programs that aim to strengthen coping strategies may be useful in preventing self-harm among adolescents.

In the study of coronary artery disease (CAD), the mechanism of plaque formation and development is still an important subject for investigation. A limitation of current coronary angiography (CAG) is that it can only show static images of the narrowing of arterial channels without identifying the mechanism of the disease or predicting its progression or regression. To address this limitation, the CAG technique has been modified. The new approach emphasizes identifying and analyzing blood flow patterns, employing methodologies akin to those used by hydraulic engineers for fluid or gas movement through domestic or industrial pipes and pumps. With the new technique, various flow patterns and arterial phenomena-such as laminar, turbulent, antegrade, retrograde, and recirculating flow and potentially water hammer shock and vortex formation-are identified, recorded, and classified. These phenomena are then correlated with the presence of lesions at different locations within the coronary vasculature. The formation and growth of these lesions are explained from the perspective of fluid mechanics. As the pathophysiology of CAD and other cardiovascular conditions becomes clearer, new medical, surgical, and interventional treatments could be developed to reverse abnormal coronary flow dynamics and restore laminar flow, leading to improved clinical outcomes.

Purinergic P2X3 receptors form trimeric cation-gated channels, which are activated by extracellular ATP. P2X3 plays a crucial role in chronic cough and affects over 10% of the population. Despite considerable efforts to develop drugs targeting P2X3, the highly conserved structure within the P2X receptor family presents obstacles for achieving selectivity. Camlipixant, a potent and selective P2X3 antagonist, is currently in phase III clinical trials. However, the mechanisms underlying receptor desensitization, ion permeation, principles governing antagonism, and the structure of P2X3 when bound to camlipixant remain elusive. In this study, we established a stable cell line expressing homotrimeric P2X3 and utilized a peptide scaffold to purify the complex and determine its structure using cryo-electron microscopy (cryo-EM). P2X3 binds to camlipixant at a previously unidentified drug-binding site and functions as an allosteric inhibitor. Structure-activity studies combined with modeling and simulations have shed light on the mechanisms underlying the selective targeting and inhibition of P2X3 by camlipixant, distinguishing it from other members of the P2X receptor family., Competing Interests: Conflict of Interest declaration: PPN, SS, IH, SA, and JS work for ELANCO. This work was funded by a grant to RS by ELANCO.

Objectives: We investigated changes over time in mental and social wellbeing indicators for vulnerable population subgroups during the pandemic. These groups were younger people, people with disabilities, low-income groups, unemployed, culturally, and linguistically diverse communities (CaLD), and Aboriginal and Torres Strait Islander peoples., Methods: A series of four repeated population representative surveys were conducted in June 2020, September 2020, January 2022, and June 2022. Questions included items on psychological distress, financial hardship, social connection, and life satisfaction., Results: For most groups, social connection and life satisfaction improved in 2022 relative to 2020. Psychological distress and financial hardship showed the opposite pattern, with some groups having worse results in 2022 relative to 2020. People without any vulnerability had better mental health and social wellbeing outcomes at each time point relative to the vulnerable population subgroups., Conclusion: Pandemic-related policies had differential effects over time and for different population groups. Future policies and research need to closely monitor how they impact population subgroups, and the overall results clearly demonstrate the inequity in mental health and social wellbeing outcomes for vulnerable population cohorts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Joyce, Tran, Stocker and Fisher.)

Purpose: To evaluate the effectiveness of the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol in ovarian stimulation., Methods: In this retrospective cohort study, we included 804 patients who were treated between January 1 st , 2022, and July 1 st , 2023. Outcomes of ovarian stimulation were compared between the PPOS (n = 206) and GnRH-ant (n = 598). The primary outcome was the number of good cleavage embryos., Results: Baseline characteristics were comparable in both groups. In both unadjusted and adjusted analysis, the mean number of good cleavage embryos in PPOS (6.33) was non-inferior to GnRH-ant (6.44; unadjusted ratio of two means 1.02, 95%CI 0.92, 1.13). The trigger-day estradiol level in patients with PPOS was higher than in patients with GnRH-ant (4,420 vs 3,830 pg/ml, respectively) despite similar total follicle stimulating hormone dose and fewer days of ovarian stimulation. The number of oocytes, MII oocytes, cleavage and blastocyst embryos were comparable between the two protocols. After the first transfer of embryos, the clinical pregnancy rate and implantation rate were higher in the PPOS group, while the pregnancy rate and ongoing pregnancy were not significantly different. None of the PPOS patients had an unexpected LH surge, and serum LH levels decreased slightly during ovarian stimulation., Conclusions: The PPOS protocol with dydrogesterone provided similar embryo outcomes to the GnRH-ant protocol, with notable distinctions in clinical pregnancy and implantation rate. The serum LH concentration during ovarian stimulation using PPOS was well-controlled., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest associated with this manuscript. There are no financial or personal relationships between any of the authors and other individuals or organizations that could inappropriately influence this work. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare that they have no competing interests. The authors alone are responsible for the writing and content of this paper. The manuscript has not been published previously, nor is it under consideration by another journal. We confirm that this manuscript complies with the journal's guidelines., (Copyright © 2023 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Kombucha, a fermented beverage, is gaining popularity due to its numerous beneficial health effects. Various substrates such as herbs, fruits, flowers, and vegetables, have been used for kombucha fermentation in order to enhance the flavor, aroma, and nutritional composition. This study aims to investigate the potential suitability of cascara as a novel ingredient for kombucha production. Our findings suggested that cascara is a suitable substrate for kombucha production. Fermentation elevated the total phenolic and flavonoid content in cascara, which enhanced the antioxidant, antibacterial, and prebiotic characteristics of the product. Furthermore, the accumulation of acetic acid-induced the pH lowering reached 2.7 after 14 days of fermentation, which achieved the microbiological safety of the product. Moreover, 14 days of fermentation resulted in a balanced amalgamation of acidity, sweetness, and fragrance according to sensory evaluation. Our findings not only highlight the potential of cascara kombucha as a novel substrate for kombucha production but also contribute to repurposing coffee by-products, promoting environmentally friendly and sustainable agricultural development.

Over the last decade, field assessments of the yellow rust differential lines for resistance genes Yr10 and Yr24 and race analysis in the Middle East have demonstrated efficient yellow rust control by Yr10 and Yr24 (=Yr26). Yellow rust samples collected during 2018-21 in Central West Asia & North and sub-Saharan Africa underwent race analysis at the Regional Cereal Rust Research Center in Izmir, Türkiye. The infected leaf segments were subjected to rehydration at 20°C for three hours. Subsequently, the leaf segments were rubbed on the first leaves of seedlings of susceptible cultivar Morocco. Inoculated seedlings were placed at 10°C in dark conditions with 95% humidity for 24 hrs, then moved to a growth chamber with a 16-hr light (220 µmolm-2s-1) cycle at 15°C and an eight-hour dark period at 12°C. Urediniospores were collected 15 days post-inoculation. A set of yellow rust differential lines including Morocco, Avocet 'S', Avocet 'R', Yr1/6* Avocet 'S', Kalyansona (Yr2), Vilmorin 23 (Yr3), Hybrid 46 (Yr4), Yr6/6* Avocet 'S', Yr7/6* Avocet 'S', Yr8/6* Avocet 'S', Yr9/6* Avocet 'S', Yr10/6* Avocet 'S', Moro (Yr10+), Yr17/6*Avocet 'S', Yr24/6* Avocet 'S', TP1295 (Yr25), Yr27/6* Avocet 'S', YrSp/6* Avocet 'S', Spalding Prolific (YrSP), Strubes Dickkopf (YrSD), Tres/6*Avocet'S', Cham 1, and Ambition was used in race analysis. A mixture of 2 mL Soltrol® and 0.5 mg fresh urediniospores was used to inoculate 10-day-old seedlings of the 23 differential varieties. Pre-inoculation, incubation, and post-inoculation conditions were the same as above. Seedling infection types (ITs) were recorded 15 days post-inoculation on a scale of 0 to 9 (McNeal et al. 1971), where ITs 0 to 6 are classified as low infection types (LITs= avirulent) and ITs 7 to 9 categorized as high infection types (HITs= virulent). HITs of 7 to 9 were observed for the first time on Yr10/6* Avocet 'S', Yr24/6* Avocet 'S', as well as on Moro (Yr10+) for 25 sample of the total 50 isolates from Lebanon and Türkiye in 2018. During the race analysis in 2019 to 2021, virulence for Yr10 and Yr24 was identified among tested samples from Egypt, Lebanon, Jordan, Syria, and Türkiye, indicating the expansion of virulence for Yr10 and Yr24 into new regions. HITs were observed for the durum wheat cultivar Cham 1 and wheat cultivar Ambition in all races. Virulence for YrA, Yr2, Yr6, Yr7, Yr8, Yr17, and 32 was common within the Yr10 and Yr24 virulent races, and virulence for YrSp and Yr27 were observed in low frequency. Molecular genotyping of 209 isolates, including the Yr10 virulent races, was performed using 19 microsatellite markers (Ali et al. 2017; Rodriguez-Algaba et al. 2017) and aligned with the Puccinia striiformis nomenclature system of the Global Rust Reference Center (GRRC). The results showed that 66 isolates were identical to the genotyping lineage "ME2018" identified in Egypt in 2018 by GRRC. This genetic lineage has now been designated as PstS17 (Hovmøller et al. 2023). The durum wheat cultivars have always been resistant to yellow rust in the Middle East. Seedling tests of 50 durum advanced lines from CIMMYT's International Durum Wheat Yield Nursery showed LITs in 45 accessions (90%) against an avirulent race for Yr10 and Yr24 (PstS2), but only 12% remained resistant while tested with a PstS17 (virulent for Yr10 and Yr24). This observation provides compelling evidence of the Yr10 and/or Yr24 presence within tested durum wheat germplasm. Continued monitoring of virulence and resistance of wheat germplasm to yellow rust is critical for successful breeding for rust resistance.

Quality control of human induced pluripotent stem cells (iPSCs) is critical to ensure reproducibility of research. Recently, KOLF2.1J was characterized and published as a male iPSC reference line to study neurological disorders. Emerging evidence suggests potential negative effects of mtDNA mutations, but its integrity was not analyzed in the original publication. To assess mtDNA integrity, we conducted a targeted mtDNA analysis followed by untargeted metabolomics analysis. We found that KOLF2.1J mtDNA integrity was intact at the time of publication and is still preserved in the commercially distributed cell line. In addition, the basal KOLF2.1J metabolome profile was similar to that of the two commercially available iPSC lines IMR90 and iPSC12, but clearly distinct from an in-house-generated ERCC6 R683X/R683X iPSC line modeling Cockayne syndrome. Conclusively, we validate KOLF2.1J as a reference iPSC line, and encourage scientists to conduct mtDNA analysis and unbiased metabolomics whenever feasible., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mitochondrial DNA (mtDNA) analysis is crucial for the diagnosis of mitochondrial disorders, forensic investigations, and basic research. Existing pipelines are complex, expensive, and require specialized personnel. In many cases, including the diagnosis of detrimental single nucleotide variants (SNVs), mtDNA analysis is still carried out using Sanger sequencing. Here, we developed a simple workflow and a publicly available webserver named Mitopore that allows the detection of mtDNA SNVs, indels, and haplogroups. To simplify mtDNA analysis, we tailored our workflow to process noisy long-read sequencing data for mtDNA analysis, focusing on sequence alignment and parameter optimization. We implemented Mitopore with eliBQ (eliminate bad quality reads), an innovative quality enhancement that permits the increase of per-base quality of over 20% for low-quality data. The whole Mitopore workflow and webserver were validated using patient-derived and induced pluripotent stem cells harboring mtDNA mutations. Mitopore streamlines mtDNA analysis as an easy-to-use fast, reliable, and cost-effective analysis method for both long- and short-read sequencing data. This significantly enhances the accessibility of mtDNA analysis and reduces the cost per sample, contributing to the progress of mtDNA-related research and diagnosis., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Older people experiencing depression and anxiety have higher rates of health service utilisation than others, but little is known about whether these influence their seeking of emergency care. The aim was to examine the associations between symptoms of depression and the use of emergency health care, in an Australian context, among a population of people aged 70 years and over initially free of cardiovascular disease, dementia or major physical disability., Methods: We undertook secondary analyses of data from a large cohort of community-dwelling Australians aged [Formula: see text]70 years. Multivariable logistic regression was used to compare the association of symptoms of depression (measured using the Center for Epidemiological Studies Depression Scale 10 question version, CESD at baseline) with subsequent episodes of emergency care, adjusting for physical and social factors of clinical interest. Marginal adjusted odds ratios were calculated from the logistic regression., Results: Data were available for 10,837 Australian participants aged at least 70 years. In a follow-up assessment three years after the baseline assessment, 17.6% of people self-reported an episode of emergency care (attended an ED of called an emergency ambulance) in the last 12 months. Use of emergency healthcare was similar for men and women (17.8% vs. 17.4% p = 0.61). A score above the cut-off on the CESD at baseline was associated with greater use of emergency health care (OR = 1.35, 95% CI 1.11,1.64). When modelled separately, there was a greater association between a score above the cut-off on the CESD and emergency healthcare for women compared with men., Conclusions: This study is unique in demonstrating how depressive symptoms among healthy older persons are associated with subsequent increased use of emergency healthcare. Improved understanding and monitoring of mental health in primary care is essential to undertake effective healthcare planning including prevention of needing emergency care., (© 2024. The Author(s).)

Amlexanox is an anti-inflammatory and anti-allergic agent used clinically for the treatment of aphthous ulcers, allergic rhinitis, and asthma. Recent studies have demonstrated that amlexanox, a selective inhibitor of IkB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1), suppresses a range of diseases or inflammatory conditions, such as obesity-related metabolic dysfunction and type 2 diabetes. However, the effects of amlexanox on neuroinflammatory responses to amlexanox have not yet been comprehensively studied. In this study, we investigated the novel therapeutic effect of amlexanox on LPS-induced neuroinflammation in vivo, and intraperitoneal injection of amlexanox markedly reduced LPS-induced IKKε levels, proinflammatory cytokines, and microglial activation, as evidenced by ionized calcium-binding adapter molecule 1 (Iba1) immunostaining. Furthermore, amlexanox significantly reduced proinflammatory cytokines and chemokines in LPS-induced bone marrow-derived macrophages (BMDM), murine BV2, and human HMC3 microglial cells. This data provided considerable evidence that amlexanox can be used as a preventive and curative therapy for neuroinflammatory and neurodegenerative diseases. In terms of mechanism aspects, our results demonstrated that the anti-inflammatory action of amlexanox in BV2 microglial cells was through the downregulation of NF-κB and STAT3 signaling pathways. In addition, the combination of amlexanox and SPI (a STAT3 selective inhibitor) showed high efficiency in inhibiting the production of neurotoxic and pro-inflammatory mediators. Overall, our data provide rational insights into the mechanisms of amlexanox as a potential therapeutic strategy for neuroinflammation-related diseases., (© 2024. The Author(s).)

Rye ( Secale cereale L .) is an important cereal crop used for food, beverages, and feed, especially in North-Eastern Europe. While rye is generally more tolerant to biotic and abiotic stresses than other cereals, it still can be infected by several diseases, including scald caused by Rhynchosporium secalis . The aims of this study were to investigate the genetic architecture of scald resistance, to identify genetic markers associated with scald resistance, which could be used in breeding of hybrid rye and to develop a model for genomic prediction for scald resistance. Four datasets with records of scald resistance on a population of 251 hybrid winter rye lines grown in 2 years and at 3 locations were used for this study. Four genomic models were used to obtain variance components and heritabilities of scald resistance. All genomic models included additive genetic effects of the parental components of the hybrids and three of the models included additive-by-additive epistasis and/or dominance effects. All models showed moderate to high broad sense heritabilities in the range of 0.31 (SE 0.05) to 0.76 (0.02). The model without non-additive genetic effects and the model with dominance effects had moderate narrow sense heritabilities ranging from 0.24 (0.06) to 0.55 (0.08). None of the models detected significant non-additive genomic variances, likely due to a limited data size. A genome wide association study was conducted to identify markers associated with scald resistance in hybrid winter rye. In three datasets, the study identified a total of twelve markers as being significantly associated with scald resistance. Only one marker was associated with a major quantitative trait locus (QTL) influencing scald resistance. This marker explained 11-12% of the phenotypic variance in two locations. Evidence of genotype-by-environment interactions was found for scald resistance between one location and the other two locations, which suggested that scald resistance was influenced by different QTLs in different environments. Based on the results of the genomic prediction models and GWAS, scald resistance seems to be a quantitative trait controlled by many minor QTL and one major QTL, and to be influenced by genotype-by-environment interactions., Competing Interests: Authors KM, MM, JO, PS and AJ were employed by the company Nordic Seed A/S. The research was conducted in a collaboration between Aarhus University and the plant breeding company Nordic Seed A/S. The funders had no role in the design of the study, in collection, analysis, or interpretation of data, or in the decision to publish the results. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Madsen, Kristensen, Mahmood, Thach, Mohlfeld, Orabi, Sarup, Jahoor, Hovmøller, Rodriguez-Algaba and Jensen.)

Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare.

Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare.

Aims: To evaluate the effects of a 5-day residential psychoeducational program on maternal anxiety and fatigue symptoms among women admitted with their unsettled infants and determine the psychological, social and demographic characteristics which are associated with the effect sizes., Methods: This is a secondary analysis of routinely collected data from mothers with children aged up to 24 months who were admitted to and completed the residential early parenting psychoeducational program at Masada Private Hospital Early Parenting Centre in Melbourne. Maternal anxiety symptoms were assessed using the Edinburgh Postnatal Depression Scale Three-item Anxiety subscale and maternal fatigue symptoms were the Modified Fatigue Assessment Scale at preadmission, predischarge and follow-up 6-weeks post discharge., Results: Overall, 1220 admissions were included in analyses. Cohen's d for reductions in the anxiety symptoms during the program was 0.64 (95% CI 0.59 to 0.70) and from pre-discharge to post-discharge was 0.14 (95% CI 0.09 to 01.9), and for fatigue was 1.21 (95% CI 1.11 to 1.32). Higher borderline personality disorder symptoms and experiencing more stressful life events were associated with lower mean reductions in anxiety and fatigue symptoms. Women with a history of mental health problems had lower anxiety symptom reductions. Women who were older or had younger babies had lower fatigue score reductions., Conclusion: This study confirms the effectiveness of a 5-day residential early parenting psychoeducational program provided by a private sector facility in reducing postnatal anxiety and fatigue rapidly, with effects maintained to at least 6-weeks post-discharge.

Importance: The relationship between self-reported walking limitation, a proxy of muscle function, and fracture risk has not been investigated., Objective: To examine the association between a self-reported walking limitation of 1000 m or less and 5-year risk of fracture., Design, Setting, and Participants: This prospective cohort study compared individuals with various degrees of walking ability limitation at 1000 m (a little limitation and a lot of limitation) and those without limitation (no limitation) accounting for age, falls, prior fractures, and weight. Participants from the ongoing population-based Sax Institute 45 and Up Study were followed from recruitment (2005-2008) for 5 years (2010-2013). Data analysis was conducted from July 2020 to September 2023., Exposure: Self-reported walking limitation., Main Outcomes and Measures: Incident fracture and site-specific fractures (hip, vertebral, and nonhip nonvertebral [NHNV] fractures)., Results: Among the 266 912 participants enrolled in the 45 and Up Study, 238 969 were included, with 126 015 (53%) women (mean [SD] age, 63 [11] years) and 112 954 (47%) men (mean [SD] age, 61 [11] years). Approximately 20% reported a degree of limitation in walking 1000 m or less at baseline (39 324 women [24%]; 23 191 men [21%]). During a mean (SD) follow-up of 4.1 (0.8) years, 7190 women and 4267 men experienced an incident fracture. Compared with participants who reported no walking limitations, a little limitation and a lot of limitation were associated with higher risk of fracture (a little limitation among women: hazard ratio [HR], 1.32; 95% CI, 1.23-1.41; a little limitation among men: HR, 1.46; 95% CI, 1.34-1.60; a lot of limitation among women: HR, 1.60; 95% CI, 1.49-1.71; a lot of limitation among men: HR, 2.03; 95% CI, 1.86-2.22). Approximately 60% of fractures were attributable to walking limitation. The association was significant for hip, vertebral, and NHNV fracture and ranged between a 21% increase to a greater than 219% increase., Conclusions and Relevance: In this cohort study of 238 969 participants, self-reported walking limitations were associated with increased risk of fracture. These findings suggest that walking ability should be sought by clinicians to identify high-risk candidates for further assessment.

Time series classification is a task which deals with temporal sequences, a prevalent data type common in domains such as human activity recognition, sports analytics and general sensing. In this area, interest in explanability has been growing as explanation is key to understand the data and the model better. Recently, a great variety of techniques (e.g., LIME, SHAP, CAM) have been proposed and adapted for time series to provide explanation in the form of saliency maps , where the importance of each data point in the time series is quantified with a numerical value. However, the saliency maps can and often disagree, so it is unclear which one to use. This paper provides a novel framework to quantitatively evaluate and rank explanation methods for time series classification . We show how to robustly evaluate the informativeness of a given explanation method (i.e., relevance for the classification task), and how to compare explanations side-by-side. The goal is to recommend the best explainer for a given time series classification dataset. We propose AMEE, a Model-Agnostic Explanation Evaluation framework, for recommending saliency-based explanations for time series classification. In this approach, data perturbation is added to the input time series guided by each explanation. Our results show that perturbing discriminative parts of the time series leads to significant changes in classification accuracy, which can be used to evaluate each explanation. To be robust to different types of perturbations and different types of classifiers, we aggregate the accuracy loss across perturbations and classifiers. This novel approach allows us to recommend the best explainer among a set of different explainers, including random and oracle explainers. We provide a quantitative and qualitative analysis for synthetic datasets, a variety of time-series datasets, as well as a real-world case study with known expert ground truth., (© The Author(s) 2024.)

Background: India is the most populous country in the world with millions of births annually. Perinatal mental disorders (PMDs) are prevalent worldwide including in India. This study was undertaken to evaluate how mental health is addressed in national maternity and mental health policies and programs in India., Methods: We conducted a systematic review of the national policies and programs in India related to maternity care and mental health. The identified policies and programs were analysed using health policy triangle framework., Results: Our search yielded 11 relevant documents and no peer reviewed publications. No specific national policy or program on maternal mental health could be identified. Universal access to health and mental health including for women and children was clearly articulated in both national mental health and maternity policies, which emphasised that access to mental health care and treatment is a fundamental right. There were few details about how the programs and policies were developed and no accounts of consultations with community members or service providers in their formation., Conclusion: National maternity and mental health policies and programs in India appear not to consider perinatal mental health. There are promising state-based initiatives, but, given the disease burden of PMDs in India, the absence of a national policy leads to unrecognized and unmet needs of women in the states without these measures. These inequalities can be effectively minimized by well implemented national policies for perinatal mental health, accompanied by evidence-based locally tailored programs and interventions across the country., Competing Interests: Declaration of Competing Interest We declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Gestational diabetes mellitus is associated with perinatal mental disorders. Effective management may reduce this risk, but there is little evidence on effects of different glycaemic treatment targets. We assessed whether tight glycaemic treatment targets compared with less-tight targets reduce the risk of poor mental health outcomes in women with gestational diabetes., Methods: This was a secondary analysis of data from women who consented to complete perinatal mental health questionnaires as participants in the TARGET Trial, a stepped-wedge cluster randomized trial in 10 hospitals in New Zealand. All hospitals initially used less tight glycaemic targets for management of gestational diabetes and were sequentially randomized, in clusters of two at 4-monthly intervals, to using tighter glycaemic targets. Data were collected from 414 participants on anxiety (6-item Spielberger State Anxiety scale), depression (Edinburgh Postnatal Depression Scale), and health-related quality of life (36-Item Short-Form General Health Survey) at the time of diagnosis (baseline), 36 weeks of gestation, and 6 months postpartum. The primary outcome was composite poor mental health (any of anxiety, vulnerability to depression, or poor mental health-related quality of life). Generalized linear mixed models were used to determine the main treatment effect with 95% confidence intervals using an intention-to-treat approach., Results: We found no differences between randomised glycaemic target groups in the primary outcome at 36 weeks' (relative risk (RR): 1.07; 95% confidence interval 0.58, 1.95) and 6 months postpartum (RR: 1.03; 0.58, 1.81). There were similarly no differences in the components of the primary outcome at 36 weeks' [anxiety (RR: 0.85; 0.44, 1.62), vulnerability to depression (RR: 1.10; 0.43, 2.83), or poor mental health-related quality of life (RR: 1.05; 0.50, 2.20)] or at 6 months postpartum [anxiety (RR:1.21; 0.59, 2.48), vulnerability to depression (RR:1.41; 0.53, 3.79), poor mental health-related quality of life (RR: 1.11; 0.59, 2.08)]., Conclusion: We found no evidence that adoption of tighter glycaemic treatment targets in women with gestational diabetes alters their mental health status at 36 weeks' gestation and at 6 months postpartum., Trial Registration: The Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12615000282583 (ANZCTR-Registration). Date of registration: 25 March 2015., (© 2023. The Author(s).)

DaxibotulinumtoxinA-lanm for injection (DAXI) is a unique US Food and Drug Administration-approved product comprising daxibotulinumtoxinA and a stabilizing excipient peptide (RTP004). DAXI has a longer-labeled shelf life (72 h) following reconstitution than other botulinum toxin type A products. Here, we report the stability and microbial control of reconstituted DAXI when stored at 2 °C-8 °C over a period of 36 days (Study 1) and 7 days (Study 2) following reconstitution with unpreserved or preserved saline. The pH and biological activity of reconstituted DAXI in the 50 U/vial and 100 U/vial formats remained stable at the final assessed time point in both preserved and unpreserved saline when refrigerated (2 °C-8 °C). No changes in recoverable 150 kDa neurotoxin (measured by enzyme-linked immunosorbent assay) were observed over 6 days of refrigeration. Bacterial growth or pathogen proliferation was not observed in DAXI reconstituted in preserved or unpreserved saline in both studies.

Denosumab (Dmab) is increasingly prescribed worldwide. Unlike bisphosphonates (BPs), its effect on mortality has yet to be well explored. This study examined the association between Dmab and all-cause mortality compared with no treatment in subjects with a fracture and BPs in subjects without a fracture. The study population was from the Sax Institute's 45 and Up Study (n = 267,357), a prospective population-based cohort with questionnaire data linked to hospital admissions (Admitted Patients Data Collection [APDC] data were linked by the Centre for Health Record Linkage), medication records (Pharmaceutical Benefits Scheme [PBS] provided by Services Australia), and stored securely (secure data access was provided through the Sax Institute's Secure Unified Research Environment [SURE]). The new-user cohort design with propensity-score (PS) matching was implemented. In the fracture cohort, Dmab and oral BP users were matched 1:2 to no treatment (Dmab: 617 women, 154 men; oral BPs: 615 women, 266 men). In the no-fracture cohort, Dmab users were matched 1:1 with oral BPs and zoledronic acid (Zol) users (Dmab:oral BPs: 479 men, 1534 women; Dmab:Zol: 280 men, 625 women). Mortality risk was measured using sex-specific pairwise multivariable Cox models. In the fracture cohort, compared with no treatment, Dmab was associated with 48% lower mortality in women (hazard ratio [HR] = 0.52, 95% confidence interval [CI] 0.36-0.72) but not in men. Oral BPs were associated with 44% lower mortality in both sexes (women HR = 0.56, 95% CI 0.42-0.77; men HR = 0.56, 95% CI 0.40-0.78). In the no-fracture cohort, compared with BPs, Dmab was associated with 1.5- to 2.5-fold higher mortality than oral BPs (women HR = 1.49, 95% CI 1.13-1.98; men HR = 2.74; 95% CI 1.82-4.11) but similar mortality to Zol. Dmab in women and oral BPs were associated with lower post-fracture mortality than no treatment. However, Dmab users had generally higher mortality than oral BP users in those without fractures. © 2023 American Society for Bone and Mineral Research (ASBMR)., (© 2023 American Society for Bone and Mineral Research (ASBMR).)

Background: Different measures of muscle strength, physical performance and body size/composition are used in various sarcopenia definitions. This study investigated which baseline measures best predict incident mortality and falls, and prevalent slow walking speed in older women and men., Materials and Methods: Data for 899 women (mean age±standard deviation, 68.7 ± 4.3 years) and 497 men (69.4 ± 3.9 years) from the Dubbo Osteoporosis Epidemiology Study 2, comprising sixty variables for muscle strength (quadriceps strength), physical performance (walking speed, timed up and go (TUG) test, sit to stand (STS) test), body size (weight, height, body mass index) and body composition (lean mass, body fat) were included. Sex-stratified Classification and Regression Tree (CART) analyses calculated baseline variable accuracy for predicting incident mortality and falls, and prevalent slow walking speed (<0.8 m/s)., Results: Over 14.5 years, 103/899 (11.5%) women and 96/497 (19.3%) men died, 345/899 (38.4%) women and 172/497 (34.6%) men had ≥1 fall, and 304/860 (35.3%) women and 172/461 (31.7%) had baseline slow walking speed (<0.8 m/s). CART models identified age and walking speed adjusted for height as the most important predictors for mortality in women, and quadriceps strength (with adjustments) as the most important predictor for mortality in men. In both sexes, STS (with adjustments) was the most important predictor for incident falls, and TUG test was the most important predictor for prevalent slow walking speed. Body composition measures were not important predictors for any outcome., Conclusions: Muscle strength and physical performance variables and cut points predict falls and mortality differently in women and men, suggesting targeted sex-specific application of selected measures may improve outcome prediction in older adults., Competing Interests: Declaration of Competing Interest BK reports consultancy/honorarium fees from the following companies/enterprises that work in the medical and/or musculoskeletal felds: Abbott Nutrition (UK); Academy of Nutrition and Dietetics (USA); AusDoc (Australian Doctor). Dr. Kirk is also supported by a research grant from TSI Pharmaceuticals. PC reports being a consultant to BioAge Labs. GD reports paid consultancy for TSI, Abbott, and Nutricia. JRC reports honoraria for educational talks and advisory boards from Amgen and research support from Amgen., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Considering equity in early childhood development (ECD) is important to ensure healthy development for every child. Equity-informative cost-effectiveness analysis can further guide decision makers to maximize outcomes with limited resources while promoting equity. This cost-effectiveness study aimed to examine the equity impacts of a multicomponent ECD intervention in rural Vietnam. We estimated the cost-effectiveness of the intervention with a 30-month time horizon from the service provider and household perspectives with equity considerations. Data were from a cluster-randomized controlled trial comparing the intervention with the local standard of care. The incremental cost-effectiveness ratios (ICERs) per child cognitive development score gained were estimated by household wealth quintile and maternal education level, adjusted for cluster effects and baseline characteristics such as maternal parity and age. A 3% discount rate was applied to costs, and non-parametric cluster bootstrapping was used to examine uncertainty around ICERs. Children in the intervention had higher cognitive development scores than those in the control arm across all subgroups. Based on intervention recurrent cost, the ICER per cognitive development score gained was lower in children from the poorest quintile (-US$6) compared to those from the richest quintile (US$16). Similarly, the ICER per cognitive development score gained was lower in children whose mothers had the lowest education level (-US$0.02) than those with mothers who had the highest education level (US$7). Even though our findings should be interpreted with caution due to the insufficient study power, the findings suggest that the intervention could promote equity while improving child cognitive development with greater cost-effectiveness in disadvantaged groups., (© The Author(s) 2023. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Introduction: Minimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia's Home Medicine Review (HMR) can reduce patients' intake of sedative/anticholinergics and improve continuity of care. This paper describes a protocol for an randomised controlled trial to determine the efficacy of an HMR service for patients who have sustained MTF., Method and Analysis: Eligible participants are as follows: ≥65 years of age, using ≥5 medicines including at least one falls risk-increasing drug, who have sustained an MTF and under treatment in one of eight Osteoporosis Refracture Prevention clinics in Australia. Consenting participants will be randomised to control (standard care) or intervention groups. For the intervention group, medical specialists will refer to a pharmacist for HMR focused on reducing falls risk predominately through making recommendations to reduce falls risk medicines, and adherence to antiosteoporosis medicines. Twelve months from treatment allocation, comparisons between groups will be made. The main outcome measure is participants' cumulative exposure to sedative and anticholinergics, using the Drug Burden Index. Secondary outcomes include medication adherence, emergency department visits, hospitalisations, falls and mortality. Economic evaluation will compare the intervention strategy with standard care., Ethics and Dissemination: Approval was obtained via the New South Wales Research Ethics and Governance Information System (approval number: 2021/ETH12003) with site-specific approvals granted through Human Research Ethics Committees for each research site. Study outcomes will be published in peer-reviewed journals. It will provide robust insight into effectiveness of a pharmacist-based intervention on medicine-related falls risk for patients with osteoporosis. We anticipate that this study will take 2 years to fully accrue including follow-up., Trial Registration Number: ACTRN12622000261718., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Intravenous magnesium sulfate administered to pregnant individuals before birth at less than 30 weeks' gestation reduces the risk of death and cerebral palsy in their children. The effects at later gestational ages are unclear., Objective: To determine whether administration of magnesium sulfate at 30 to 34 weeks' gestation reduces death or cerebral palsy at 2 years., Design, Setting, and Participants: This randomized clinical trial enrolled pregnant individuals expected to deliver at 30 to 34 weeks' gestation and was conducted at 24 Australian and New Zealand hospitals between January 2012 and April 2018., Intervention: Intravenous magnesium sulfate (4 g) was compared with placebo., Main Outcomes and Measures: The primary outcome was death (stillbirth, death of a live-born infant before hospital discharge, or death after hospital discharge before 2 years' corrected age) or cerebral palsy (loss of motor function and abnormalities of muscle tone and power assessed by a pediatrician) at 2 years' corrected age. There were 36 secondary outcomes that assessed the health of the pregnant individual, infant, and child., Results: Of the 1433 pregnant individuals enrolled (mean age, 30.6 [SD, 6.6] years; 46 [3.2%] self-identified as Aboriginal or Torres Strait Islander, 237 [16.5%] as Asian, 82 [5.7%] as Māori, 61 [4.3%] as Pacific, and 966 [67.4%] as White) and their 1679 infants, 1365 (81%) offspring (691 in the magnesium group and 674 in the placebo group) were included in the primary outcome analysis. Death or cerebral palsy at 2 years' corrected age was not significantly different between the magnesium and placebo groups (3.3% [23 of 691 children] vs 2.7% [18 of 674 children], respectively; risk difference, 0.61% [95% CI, -1.27% to 2.50%]; adjusted relative risk [RR], 1.19 [95% CI, 0.65 to 2.18]). Components of the primary outcome did not differ between groups. Neonates in the magnesium group were less likely to have respiratory distress syndrome vs the placebo group (34% [294 of 858] vs 41% [334 of 821], respectively; adjusted RR, 0.85 [95% CI, 0.76 to 0.95]) and chronic lung disease (5.6% [48 of 858] vs 8.2% [67 of 821]; adjusted RR, 0.69 [95% CI, 0.48 to 0.99]) during the birth hospitalization. No serious adverse events occurred; however, adverse events were more likely in pregnant individuals who received magnesium vs placebo (77% [531 of 690] vs 20% [136 of 667], respectively; adjusted RR, 3.76 [95% CI, 3.22 to 4.39]). Fewer pregnant individuals in the magnesium group had a cesarean delivery vs the placebo group (56% [406 of 729] vs 61% [427 of 704], respectively; adjusted RR, 0.91 [95% CI, 0.84 to 0.99]), although more in the magnesium group had a major postpartum hemorrhage (3.4% [25 of 729] vs 1.7% [12 of 704] in the placebo group; adjusted RR, 1.98 [95% CI, 1.01 to 3.91])., Conclusions and Relevance: Administration of intravenous magnesium sulfate prior to preterm birth at 30 to 34 weeks' gestation did not improve child survival free of cerebral palsy at 2 years, although the study had limited power to detect small between-group differences., Trial Registration: anzctr.org.au Identifier: ACTRN12611000491965.

Introduction: When, in the judgment of a mental health professional, patient suicide risk and/or patient violence risk are considered imminent, they have been referred to as behavioral emergencies. Past surveys have suggested that education and training with these emergency situations have been inadequate. The present study was undertaken to obtain more current information on the training that psychologists receive in these areas of practice., Method: All directors of APA-accredited graduate psychology programs and all directors of APA-accredited predoctoral psychology internship programs were asked to complete an online survey inquiring about such training provided in their programs., Results: Results indicated that both sets of directors rated such doctoral training in suicide risk assessment and management as very important. Internship directors, however, were significantly more likely than graduate program directors to state that psychologists should be required to complete continuing education courses on other-directed violence risk. Serious gaps in training were identified; that is, only 59.2% of psychology graduate directors reported that their program offered training in safety planning for suicide risk and only 25.4% reported that their program offered training in safety planning for violence risk., Conclusion: Given that serious injury and even death can occur from patient suicidal behavior and/or a patient violent behavior, the implications of these findings are discussed., (© 2023 The Authors. Suicide and Life-Threatening Behavior published by Wiley Periodicals LLC on behalf of American Association of Suicidology.)

Data on mortality trends in patients with acute myocardial infarction (AMI) with cardiogenic shock (CS) are scant. This study aimed to assess the trends in CS-AMI-related mortality in United States (US) subjects over the latest 21 years. Mortality data of US subjects with AMI listed as the underlying cause of death and CS as contributing cause were obtained from the Centers for Disease Control and Prevention WONDER (Wide-Ranging Online Data for Epidemiologic Research) dataset from January 1999 to December 2019. CS-AMI-related age-adjusted mortality rates (AAMRs) per 100,000 US population were stratified by gender, race and ethnicity, geographic areas, and urbanicity. Nationwide annual trends were assessed as annual percent change (APC) and average APC with relative 95% confidence intervals (CIs). Between 1999 and 2019, CS-AMI was listed as the underlying cause of death in 209,642 patients, (AAMR of 3.01 per 100,000 people [95% CI 2.99 to 3.02]). AAMR from CS-AMI remained stable from 1999 to 2007 (APC -0.2%, [95% CI -2.0 to 0.5], p = 0.22) and then significantly increased (APC 3.1% [95% CI 2.6 to 3.6], p <0.0001), especially in male patients. Starting in 2009, the AAMR increase was more pronounced in those <65 years, Black Americans, and residents of rural areas. The higher AAMRs were clustered in the South (average APC 4.5%, [95% CI 4.4 to 4.6]) of the country. In conclusion, CS-AMI-related mortality in US patients increased from 2009 to 2019. Targeted health policy measures are needed to address the rising burden of CS-AMI in US subjects., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Gestational diabetes mellitus (GDM) is linked to the dysregulation of inflammatory markers in women with GDM compared to women without. It is unclear whether the intensity of glycemic control influences these biomarkers. We aimed to assess whether different glycemic targets for women with GDM and compliance influence maternal and infant biomarkers., Methods: Maternity hospitals caring for women with GDM were randomized in the TARGET Trial to tight or less tight glycemic targets. Maternal blood was collected at study entry, 36 weeks' gestation, and 6 months postpartum, and cord plasma after birth. We assessed compliance to targets and concentrations of maternal serum and infant biomarkers., Results: Eighty-two women and infants were included in the study. Concentrations of maternal and infant biomarkers did not differ between women assigned to tighter and less tight glycemic targets; however, concentrations were altered in maternal serum leptin and CRP and infant cord C-peptide, leptin, and IGF in women who complied with tighter targets., Conclusions: Use of tighter glycemic targets in women with GDM does not change the concentrations of maternal and infant biomarkers compared to less tight targets. However, when compliance is achieved to tighter targets, maternal and infant biomarkers are altered., Impact: The use of tighter glycemic targets in gestational diabetes does not result in changes to maternal or cord plasma biomarkers. However, for women who complied with tighter targets, maternal serum leptin and CRP and infant cord C-peptide, leptin and IGF were altered compared with women who complied with the use of the less tight targets. This article adds to the current evidence base regarding the impact of gestational diabetes on maternal and infant biomarkers. This article highlights the need for further research to assess enablers to meet the tighter target recommendations and to assess the impact on relevant biomarkers., (© 2023. The Author(s).)

Background: Economic evaluations are critical to ensure effective resource use to implement and scale up child development interventions. This study aimed to estimate the cost-effectiveness of a multicomponent early childhood development intervention in rural Viet Nam., Methods: We did a cost-effectiveness study alongside a cluster-randomised trial with a 30-month time horizon. The study included 669 mothers from 42 communes in the intervention group, and 576 mothers from 42 communes in the control group. Mothers in the intervention group attended Learning Clubs sessions from mid-pregnancy to 12 months after delivery. The primary outcomes were child cognitive, language, motor, and social-emotional development at age 2 years. In this analysis, we estimated the incremental cost-effectiveness ratios (ICERs) of the intervention compared with the usual standard of care from the service provider and household perspectives. We used non-parametric bootstrapping to examine uncertainty, and applied a 3% discount rate., Findings: The total intervention cost was US$169 898 (start-up cost $133 692 and recurrent cost $36 206). The recurrent cost per child was $58 (1 341 741 Vietnamese dong). Considering the recurrent cost alone, the base-case ICER was $14 and mean ICER of 1000 bootstrap samples was $14 (95% CI -0·48 to 30) per cognitive development score gained with a 3% discount rate to costs. The ICER per language and motor development score gained was $22 and $20, respectively, with a 3% discount rate to costs., Interpretation: The intervention was cost-effective: the ICER per child cognitive development score gained was 0·5% of Viet Nam's gross domestic product per capita, alongside other benefits in language and motor development. This finding supports the scaling up of this intervention in similar socioeconomic settings., Funding: Australian National Health and Medical Research Council and Grand Challenges Canada., Translation: For the Vietnamese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: Fracture risk is elevated in some type 2 diabetes patients. Bone fragility may be associated with more clinically severe type 2 diabetes, although prospective studies are lacking. It is unknown which diabetes-related characteristics are independently associated with fracture risk. In this post-hoc analysis of fracture data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (ISRCTN#64783481), we hypothesised that diabetic microvascular complications are associated with bone fragility., Materials and Methods: The FIELD trial randomly assigned 9795 type 2 diabetes participants (aged 50-75 years) to receive oral co-micronised fenofibrate 200 mg (n = 4895) or placebo (n = 4900) daily for a median of 5 years. We used Cox proportional hazards models to identify baseline sex-specific diabetes-related parameters independently associated with incident fractures., Results: Over 49,470 person-years, 137/6138 men experienced 141 fractures and 143/3657 women experienced 145 fractures; incidence rates for the first fracture of 4∙4 (95% CI 3∙8-5∙2) and 7∙7 per 1000 person-years (95% CI 6∙5-9∙1), respectively. Fenofibrate had no effect on fracture outcomes. In men, baseline macrovascular disease (HR 1∙52, 95% CI 1∙05-2∙21, p = 0∙03), insulin use (HR 1∙62, HR 1∙03-2∙55, p = 0∙03), and HDL-cholesterol (HR 2∙20, 95% CI 1∙11-4∙36, p = 0∙02) were independently associated with fracture. In women, independent risk factors included baseline peripheral neuropathy (HR 2∙04, 95% CI 1∙16-3∙59, p = 0∙01) and insulin use (HR 1∙55, 95% CI 1∙02-2∙33, p = 0∙04)., Conclusions: Insulin use and sex-specific complications (in men, macrovascular disease; in women, neuropathy) are independently associated with fragility fractures in adults with type 2 diabetes., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: The drug-eluting stent was a significant stride forward in the development of enhanced therapeutic therapy for coronary intervention, with three generations of increased advancement. VSTENT is a newly developed stent manufactured in Vietnam that aims to provide coronary artery patients with a safe, effective, and cost-efficient option. The purpose of this trial was to determine the efficacy and safety of a new bioresorbable polymer sirolimus-eluting stent called VSTENT., Methods: This is a prospective, cohort, multicenter research in 5 centers of Vietnam. A prespecified subgroup received intravascular ultrasound (IVUS) or optical coherence tomography (OCT) imaging. We determined procedure success and complications during index hospitalization. We monitored all participants for a year. Six-month and 12-month rates of major cardiovascular events were reported. All patients had coronary angiography after 6 months to detect late lumen loss (LLL). Prespecified patients also had IVUS or OCT performed., Results: The rate of device success was 100% (95% CI: 98.3-100%; P<0.001). Major cardiovascular events were 4.7% (95% CI: 1.9-9.4%; P<0.001). The LLL over quantitative coronary angiography (QCA) was 0.08±0.19 mm (95% CI: 0.05-0.10; P<0.001) in the in-stent segment and 0.07±0.31 mm (95% CI: 0.03-0.11; P=0.002) in 5 mm within the two ends of the stent segment. The LLL recorded by IVUS and OCT at 6 months was 0.12±0.35 mm (95% CI: 0.01-0.22; P=0.028) and 0.15±0.24 mm (95% CI: 0.02-0.28; P=0.024), respectively., Conclusions: This study's device success rates were perfect. IVUS and OCT findings on LLL were favorable at 6-month follow-up. One-year follow-up showed low in-stent restenosis (ISR) and target lesion revascularization (TLR) rates, reflecting few significant cardiovascular events. VSTENT's safety and efficacy make it a promising percutaneous intervention option in developing nations., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-22-522/coif). The authors have no conflicts of interest to declare., (2023 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Type 2 diabetes (T2D) may be associated with increased risk of fractures, despite preserved bone mineral density (BMD). Obesity and insulin resistance (IR) may have separate effects on bone turnover and bone strength, which contribute to skeletal fragility. We characterized and assessed the relative associations of obesity, body composition, IR, and T2D on bone turnover markers (BTMs), BMD, and advanced hip analysis (AHA). In this cross-sectional analysis of Dubbo Osteoporosis Epidemiology Study, 525 (61.3% women) participants were grouped according to T2D, IR (homeostasis model assessment insulin resistance [HOMA-IR] 2 ): insulin-sensitive lean (IS-L), insulin-sensitive overweight/obese (IS-O), insulin-resistant (IR), and T2D. BMD, AHA, and body composition, including visceral adipose tissue (VAT) (on dual-energy x-ray absorptiometry scan) and fasting BTMs, were assessed. Analyses performed using Bayesian model averaging and principal component analysis. T2D was associated with low BTMs (by 26%-30% [95% confidence interval [CI] 11%-46%] in women, 35% [95% CI 18%-48%] in men compared to IS-L), which persisted after adjustment for VAT. BTMs were similar among IR/IS-O/IS-L. BMD was similar among T2D/IR/IS-O; BMD was low only in IS-L. All groups were similar after adjustment for BMI. Similarly, AHA components were lowest in IS-L (attenuated following adjustment). On multivariate analysis, T2D was independently associated with BTMs. IR was also associated with C-terminal telopeptide of type 1 collagen in men. Age and body size were the strongest independent contributors to BMD and AHA. VAT was inversely associated with section modulus, cross-sectional area, cross-sectional moment of inertia in women, and hip axis length in men. Low bone turnover is associated with T2D and IR (in men), while BMD and hip strength/geometry are predominantly associated with body size. VAT, indicative of dysglycemia, is also associated with impaired bone geometry. Establishing the role of BTMs and AHA fracture risk may improve skeletal assessment in T2D people. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Introduction: Natural hazards are damaging environmental events, such as fires, droughts and floods, which have negative impacts on human lives, livelihoods and health. Natural hazards are increasing in intensity and severity, and may potentially have harmful effects on the health and development of children who experience them. There are few syntheses of the evidence about the effects of natural hazards on the early development of children aged from birth to 5 years old. The aim of this systematic review and meta-analysis is to determine the impact of natural hazards on the cognitive, motor, language, social and emotional development of children from birth to 5 years old., Methods and Analysis: Comprehensive searches will be conducted in five bibliographic databases: Ovid MEDLINE, Ovid PsycInfo, CINAHL Plus, Scopus and Ovid EMBASE, using predefined search terms to identify the relevant studies. The review will follow the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies will be included if they report on the association between exposure to natural hazards and at least one indicator of early childhood development (ECD). Extracted data will include: main study findings, characteristics of the study design, measures of natural hazards and ECD indicators. Observational studies with cross-sectional, case-control, prospective or retrospective cohort designs will be included in this review. Case descriptions and qualitative studies will be excluded. Study quality will be assessed using the Joanna Brigg's Institute critical appraisal tools. We will conduct a meta-analysis if the reviewed studies are sufficiently homogeneous according to research design, exposure, participants and outcome measures. The meta-analysis will include subgroup analyses (eg, length of exposure to natural hazard, type of natural hazard, ECD indicator)., Ethics and Dissemination: The findings will be disseminated through a peer-review publication, policy brief, technical report and report published on institutional stakeholder websites., Prospero Registration Number: CRD42022331621., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study aimed to examine how equity is integrated into economic evaluations of early childhood development interventions in low-and middle-income countries (LMICs), and to narratively synthesize the study characteristics and findings., Methods: We conducted a scoping review by searching three electronic databases with terms including equity, early childhood development intervention, economic evaluation, and LMICs. Interventions that aimed to improve child cognitive, physical, language, motor, or social and emotional development through health, nutrition, security and safety, responsive caregiving, and early learning interventions between conception and age 8 years were considered. Studies published in English peer-reviewed journals in the year 2000 and later were included., Results: The review included 24 cost-effectiveness studies out of 1460 identified articles based on eligibility criteria. The included studies addressed health, nutrition, social protection, and water, sanitation and hygiene interventions for child development. The common type of intervention was immunization. Mostly, equity was measured using household wealth or geographic areas, and the study findings were presented through subgroup analyses. The study settings were LMICs, but most studies were conducted by research teams from high-income countries. Overall, 63% of included studies reported that early childhood development interventions improved equity with greater intervention benefits observed in disadvantaged groups., Conclusions: Consideration of equity in evaluations of early childhood interventions provides a more complete picture of cost-effectiveness, and can improve equity. Greater focus on promoting equity consideration, multi-sectoral interventions, and researchers in LMICs would support evidence-based interventions and policies to achieve equity in child development., (© 2023. The Author(s).)

Background: Fragility fracture is associated with an increased risk of mortality, but mortality is not part of doctor-patient communication. Here, we introduce a new concept called 'Skeletal Age' as the age of an individual's skeleton resulting from a fragility fracture to convey the combined risk of fracture and fracture-associated mortality for an individual., Methods: We used the Danish National Hospital Discharge Register which includes the whole-country data of 1,667,339 adults in Denmark born on or before January 1, 1950, who were followed up to December 31, 2016 for incident low-trauma fracture and mortality. Skeletal age is defined as the sum of chronological age and the number of years of life lost (YLL) associated with a fracture. Cox's proportional hazards model was employed to determine the hazard of mortality associated with a specific fracture for a given risk profile, and the hazard was then transformed into YLL using the Gompertz law of mortality., Results: During the median follow-up period of 16 years, there had been 307,870 fractures and 122,744 post-fracture deaths. A fracture was associated with between 1 and 7 years of life lost, with the loss being greater in men than women. Hip fractures incurred the greatest loss of life years. For instance, a 60-year-old individual with a hip fracture is estimated to have a skeletal age of 66 for men and 65 for women. Skeletal Age was estimated for each age and fracture site stratified by gender., Conclusions: We propose 'Skeletal Age' as a new metric to assess the impact of a fragility fracture on an individual's life expectancy. This approach will enhance doctor-patient risk communication about the risks associated with osteoporosis., Funding: National Health and Medical Research Council in Australia and Amgen Competitive Grant Program 2019., Competing Interests: TT, TH, DB, LH, PV No competing interests declared, BA has received institutional research grants from UCB, Kyowa-Kirin and Pharmacosmos; consulting fees from UCB and Kyowa-Kirin; and fees for lectures from Amgen, Gedeon-Richter, Kyowa-Kirin, Eli Lily and Pharmacosmos. The author is also on the Advisory Board for UCB and is president of European Calcified Tissue Society. The author has no other competing interests to declare, JC has received honoraria for educational talks and Advisory boards from Amgen and honoraria for an Advisory board from Bayer. The author has no other competing interests to declare, TN has received grants from Australian National Health and Medical Research Council and Amgen Competitive Grant Program; fees for lectures from Amgen, Bridge Health Care (VN), DKSH Pharma, MSD and VT Health Care (VN); and support from Amgen for attending the annual meeting of APCO and from VT Health Care (VN) for attending the Vietnam Osteoporosis Society Annual Scientific Meeting. The author is also Chair of the Research Committee for Australian and New Zealand Bone and Mineral Society, a Senior Advisor for Vietnam Osteoporosis Society, and an Executive Member of Asia Pacific Consortium on Osteoporosis. The author has no other competing interests to declare, (© 2023, Tran et al.)

As, Pb and Hg are common environmental contaminants in low- and middle-income countries. We investigated the association between child toxicant exposure and growth and development and determined if this association was mitigated by Se concentration. Toxicant concentrations in fingernail samples, anthropometry and Bayley's Scales of Infant Development, 3rd edition domains were assessed in 36-month-old children whose mothers had been part of a randomised controlled trial in rural Vietnam. Multivariable regression analyses were performed to estimate the effect of toxicant exposure on clinical outcomes with adjustments for potential confounders and interaction with fingernail Se concentration. We analysed 658 children who had data for at least one physical or developmental outcome, and at least one toxicant measurement, and each of the covariates. Fingernail As concentration was negatively associated with language (estimate per 10 % increase in As: -0·19, 95 % CI: (-0·32, -0·05)). Pb was negatively associated with cognition (estimate per 10 % increase in Pb: -0·08 (-0·15, -0·02)), language (estimate per 10 % increase in Pb: -0·18 (-0·28, -0·10)) and motor skills (estimate per 10 % increase in Pb: -0·12 (-0·24, 0·00)). Hg was negatively associated with cognition (estimate per 10 % increase in Hg: -0·48, (-0·72, -0·23)) and language (estimate per 10 % increase in Hg -0·51, (-0·88, -0·13)) when Se concentration was set at zero in the model. As Se concentration increased, the negative associations between Hg and both cognition and language scores were attenuated. There was no association between toxicant concentration and growth. As, Pb and Hg concentrations in fingernails of 3-year-old children were associated with lower child development scores. The negative association between Hg and neurological development was reduced in magnitude with increasing Se concentration. Se status should be considered when assessing heavy metal toxicants in children and their impact on neurodevelopmental outcomes.